Bial-Portela Drug Trial Halted When 6 Are Hospitalized; One Person Is Brain Dead

Clinical testing on an experimental drug from Bial-Portela & Ca. SA, a closely held Portuguese company, led to six patients being hospitalized in France including one person who was put on life support and diagnosed as brain dead.

Three of the 90 people who took the drug in the early-stage trials that began in July may suffer irreversible harm, Gilles Edan, a doctor at the hospital in Rennes in north-western France, said in a televised briefing on Friday. The six hospitalized patients were those who took the drug repeatedly starting Jan. 7, according to Marisol Touraine, the French minister for health, who called it an accident of “extraordinary gravity.” The testing was stopped on Jan. 11.

French authorities plan to begin an investigation into the trial conditions, and all the enrolled volunteers are being contacted, Touraine told reporters. While serious side effects can occur in the first stage of testing drugs in humans — which typically involves giving the medicine to a small number of healthy people to see if it’s safe — incidents such as the one in France are “extremely rare,” according to Monika Benstetter, a spokeswoman for the European Medicines Agency. A decade ago in London, six healthy men suffered multiple organ failures after taking an experimental medicine.

Unprecedented Event

“What we are seeing today is without precedent,” Touraine told reporters. “We haven’t found any such accident for a trial in phase 1 in our records.”

Bial’s experimental drug aims to treat mood and motor disorders linked to neurodegenerative illnesses and anxiety. There’s no known antidote for the treatment, which acts on systems in the body that respond to pain, Touraine said. The drug doesn’t contain cannabis and isn’t derived from cannabis either, she said.

The participants in the trial conducted by Biotrial were healthy volunteers, with the drug being taken orally. The six patients affected, all men 28 to 49 years old, were taken to the hospital in Rennes, with the first arriving there on Sunday. Three of them show lesions that could potentially be irreversible, the doctor said. The health ministry was informed of the incident on Thursday night.

Investigating Cause

Bial said its employees are in Rennes cooperating with authorities. The drugmaker’s main concern now is monitoring the participants in the trial and ensuring their well being, as well as finding out the cause of the adverse reaction, according to a statement from Bial. It said 108 healthy volunteers had already participated in the tests without any moderate or serious adverse reactions becoming evident.

“Clearly, they didn’t do enough pre-clinical testing,” Asthika Goonewardene, an analyst at Bloomberg Intelligence, said by phone.

In the 2006 trial in the U.K., German drugmaker TeGenero AG was evaluating a monoclonal antibody for the treatment of rheumatoid arthritis and leukemia. The company later declared bankruptcy. The BMJ, formerly the British Medical Journal, reported in April that a clinical trial of the same treatment was scheduled to begin in Russia for rheumatoid arthritis.

In Europe, approval of clinical trials is handled by country regulators — in this case, France’s ANSM — not the EMA, Benstetter said. ANSM authorized the trial on June 26.

Bial said the compound is a new molecule that works by inhibiting the FAAH enzyme, which helps regulates the body’s ability to sense potential harm. Drugmakers are testing FAAH inhibitors for a range of nervous-system disorders including anxiety, alcoholism and pain.

–With assistance from Kristen Hallam, Phil Serafino and Joao Lima.